Sunday, April 02, 2006

Why the BU Lab is Not Important or Needed in Boston

The author, a former biotechnology executive,currently consults on biotechnology andpharmaceutical strategy to many kinds of businessclients.

Boston University's proposed laboratory complexis to house a "Biosafety Level" BSL4 laboratory,the numeral "4" designating the highest level ofbiohazard security. (Other levels are BSL3s,which study pathogens like anthrax for whichthere are treatments, and BSL2s, which houseless-threatening infectious disease agents.)BSL4s experiment only on the most dangerousdisease agents usually not endemic to the US likethe hemorrhagic fever viruses, Ebola and Marburg.At present, only a very few highly exoticpathogens qualify for BSL4.

One of Boston University's main arguments for theBSL4 is that it is vital to Boston's economy andbioscience communities - these composed of majorpharmaceutical companies, biotechnologycompanies, and academic and other non commerciallabs. I don't believe BU's claim. Of the ten orso major pharmaceutical company facilities, themore than 200 biotechnology companies, andhundreds of infectious- disease non-commercialresearch labs in Massachusetts, perhaps only ahandful will ever use the BSL4 lab at BostonUniversity. Indeed, failure to build the BSL4will cause at most a hiccup in the area’sbioscience industry.

To understand why this is so, consider the majorinternational disease threats that won't bestudied at the BSL4: malaria, HIV/AIDS, andtuberculosis. All three require only BSL2 levelcontainment since they are already present in thepopulation and there’s no need to protect thepublic from exposure to them from escape from thelaboratory. The same is true for the vastmajority of infectious disease agents endemic tothe U.S. The deadly 1957 and 1968 influenzastrains require only BSL3 containment, eventhough they are not currently present in thepopulation. The recently resurrected pandemic 1918 strain requires containment between BSL3 and BSL4 (though it should require BSL4 containment.)

A closer look at the different parts of theMassachusetts bioscience community reveals whythe Boston University BSL4 would be - at verybest - redundant, as there are already four BSL4selsewhere in the country.

Major pharmacetical companies

The modern pharmaceutical industry, composed ofthe 40-odd companies comprising the member listof the Pharmaceutical Research and ManufacturersAssociation, cut its teeth on antibioticdevelopment in the 1950s and 1960s. They hadconsiderable expertise in developing"countermeasures" - biodefense language forantibiotics, antivirals, vaccines and other suchagents - against natural disease. But lately ithas been far more profitable for companies todrift away from antibiotic development, focusinginstead on drugs for chronic conditions like highcholesterol and depression. Sold over and overagain to patients, these drugs have sales of wellover an annual $1 billion. By contrast,biodefense "countermeasure" sales will usually beone-time sales to the Strategic NationalStockpile only representing a few hundred milliondollars at most.

There are other reasons why the companies areunlikely to make use of the BU facility forbiodefense research:

Liability: Concerns over law suits from possibleuse of non FDA approved drugs during emergencies.

Damage to their reputations: Concerns oversickness or death from use of drugs, FDA-approvedor not, in false-alarm emergencies. The industrylikely would not want to see untested drugs usedat all.

Bad publicity: Working with biological weaponsagents, for whatever reason, makes for badpublicity. The US public and our enemies, oftensuspicious of the industry’s motives, couldmistake defensive research for offensivebioweapons development. The industry stressesthat “Disease is our enemy. Working to save livesis our job.”

Increased inspections and oversight: The industryalready feels over-inspected by the government.Possession and work with biological weaponsagents will require considerable paper work,security clearances, and oversight by thegovernment. In any mishap, an FBI investigationcould result – for a company, to be avoided atall costs.

Confidentiality: Pharmaceutical companies aresecretive; they dislike any disclosure they deeminappropriate or premature. So a company isunlikely to be attracted by a facility located ina context with a large population of studentswith no financial stake in their company. Theinability to guarantee confidentiality will be adisincentive to a company.

Here are some additional observations. TheBioShield 2004 legislation provides for the useof non-FDA- approved countermeasures in anemergency -- countermeasures that may never havebeen tested in humans. The pharmaceuticalindustry won’t support any BioShield legislationwhen they’re not protected from liability forharm caused by haphazard use of their drugs. Andwhile Senator Bill Frist has attached an immunityclause to a large biodefense bill soon to pass,it’s unlikely that the immunity provision willsurvive very long. Many Congress members havebeen putting up stiff resistance to letting majorcorporations off the hook by granting themimmunity from lawsuits.

Ebola and the like have no natural incidence inthe US. For a market large enough to catch amajor pharmaceutical company’s interest, adisease must be prevalent in the population orhighly expensive to maintain patients, diseasesstudied in BSL2s not BSL4s. There are plenty ofBSL2s: most laboratories doing infectious diseaseresearch have them. Moreover, for reasons ofconfidentiality, major pharmaceutical companiescan easily afford and are likelier to preferhaving their own BSL2 labs.

Biotechnology companies

Biotechnology companies are different from theforty- odd major pharmaceutical companies: theyhave no products on the market and they arestruggling financially. For them, a one-time saleworth several million dollars to the so-calledStrategic National Stockpile could be attractive.Some biotechnology companies, drawn to antibioticmarkets, are applying their novel research skillsto infectious disease.

There are about 275 Massachusetts biotechcompanies profiled by the MassachusettsBiotechnology Council [MBC.] Seventeen of thesesay they are engaging in research and developmentof infectious disease therapies. Only one companydescribes itself as conducting defense research-- developing rapid means of identifyingpathogens. Only three companies identifythemselves as vaccine companies. Of these, onlyone, Acambis, is actually developing abio-defense vaccine, which is for smallpox. Thus,from their MBC descriptions, none of theseventeen companies appears to need a BSL4facility.

If the Boston University BSL4 laboratory were notbuilt, perhaps none, but at most only a few ofthe 275 Massachusetts biotechnology companieswould be affected. Those few would have to goelsewhere to do final experiments. Moreover, thebiotechnology industry took root arounduniversities in Boston and San Francisco, notaround the extant BSL4 facilities in Maryland andAtlanta. Cambridge has no BSL4 laboratory, and alaw prohibiting rDNA research in BSL4laboratories, yet that city has a significantbiotechnology company presence.

Academic and other non-commercial labs

There may well be over a hundred academiclaboratories carrying out infectious diseaseresearch in the Boston area. A few quick PubMedsearches using key words such as “filovirus,”“Ebola,” “Marburg,” “biodefense,” “bioter ror,”“smallpox,” and the like, yield between 3 and 30hits for each key word in the Boston-area. Abrief examination of titles and abstracts of thePub Med hits reveals that only a few are actualresearch papers. Most are commentaries on generalareas like history, policy, and epidemiology.

So there seems to be little academic researchactivity in the Boston area that would require aBSL4 laboratory. Of course, some scientists at BUand other surrounding universities plan researchin the BSL-4 laboratory. The BU-NIH grantapplication to build the facility includes 43resumes. Some of these came from administrators.Some were from scientists who could "benefit"from the lab, others were unclear about how theywould use the lab

A final comment: outbreaks of the filoviruseswhich are prominent in the handful of exoticdiseases to be studied in BSL4s, have beenlocalized on their continent of origin, Africa.Ebola and Marburg, two of the dreaded hemorrhagicfever viruses, are among the filoviruses. Butwhile death from them is horrific, outbreakscause deaths in the tens to hundreds, notmillions. Thus they have not representedinternational public health threats. Apparently,they do not pose biological weapon threats to theUS, either. Government biodefense researchers atUSAMRIID have stated that most evidence suggeststhey aren’t very stable by aerosol dissemination,the only mechanism that would make them abioweapons threat. Since there are so few ofthese agents and existing BSL4 labs are workingon them, a Boston- area laboratory would beredundant, hardly the necessity its proponentsclaim. There is no reason that work on theseagents cannot be carried out in the four existingBSL4 facilities.